The 43-year-old has signed a four-year deal and replaces Danny Cowley, who left to become Huddersfield boss last week.
Lincoln said on their Twitter account: “The Imps are delighted to announce the appointment of Michael Appleton as Lincoln City’s new first team manager.”
Chairman Clive Nates added: “Michael has all the qualities we have been searching for to continue our progress as a club.”
Appleton has previous managerial experience with Portsmouth, Blackpool, Blackburn and Oxford.
Lincoln achieved two promotions in three seasons under Cowley and are currently ninth in League One, although they have picked up just one point from their last three games ahead of Saturday’s visit of Oxford.
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